Because of the large volume of saliva secreted daily by the salivary glands and their ready accessibility, the glands may be useful for the delivery of therapeutic proteins to the oral cavity and upper alimentary tract. Such an approach would take advantage of recent developments in gene transfer technology. At the same time, there is a general lack of data concerning the regulation of normal gene expression in the salivary glands. Hence, the objectives of this project are; (I) to develop and improve techniques for in vivo gene transfer, (II) to use in vivo gene transfer for the study of salivary gland gene expression and (III) to develop gene-based strategies for the treatment of oro-pharyngeal and salivary gland diseases. These studies are derived from our earlier observations that adenovirus vectors could be used to transfer exogenous genes to rat salivary glands in situ. Furthermore, the vectors can direct the synthesis of secretory proteins that can be secreted at high levels in the saliva. While current adenovirus vectors provide only transient gene expression, they have been useful in characterizing the promoter of rat GRP. We have also found that at least some salivary-specific promoters maintain their characteristics when they are put into adenovirus vectors. In the future, we hope to use salivary gland gene transfer to overexpress the anticandidal protein, histatin, in the saliva of patients with mucosal candidiasis.